The story revolves around Delirium's wish to reconcile with her brother Destruction. To this end, she first contacts Desire and Despair, each of whom refuse to accompany her on her quest; and finally persuades Dream. According to her list, they consult people who knew Destruction; but each time these people are destroyed (such as a 15,000-year-old lawyer killed by part of a building falling on him), or driven into hiding (such as the Alder Man, who changes himself into a bear and has his shadow assume his appearance). After their driver, Ruby DeLonge, dies in a fire caused by smoking in bed, Dream has his raven Matthew help Delirium drive their car to a strip club, where Dream consults with Ishtar, a former lover of Destruction. After Dream, Delirium, and Matthew leave, Ishtar performs a furious dance, in which she and the club are destroyed. Realising that the various deaths are caused by their quest, Dream refuses to continue. Delirium secludes herself, and Dream converses with the goddess Bast. Later, Death scolds Dream into accompanying Delirium again. Therefore Dream and Delirium visit Destiny, who redirects them anew. As they leave, Destiny's book shows a flashback in which Destruction abandoned his realm, as well as a scene showing Dream returning to Earth just prior to his imprisonment; Death visiting a young boy in China; and and a white-robed Dream talking with the Corinthian. At Destiny's advice, Dream visits his son Orpheus, who directs them to Destruction in a small cabin, where he makes paintings and writes poetry, criticised by his dog Barnabas.
During dinner, Destruction reveals that rather than allowing himself to be destroyed and have another aspect of himself take over - as had previously happened to Despair - he decided to abandon his realm. Destruction also admits that he placed safeguards up in case someone came looking for him; these safeguards were responsible for the accidents that befell the people who knew him. As they all walk out to view the night sky, Destruction reveals that he once had a conversation with Death, who claimed that everything is already known to everyone, but they all wilfully choose to ignore this information. At length, Destruction dismantles his gallery, shrinks his scrying pool and sword, and asks that Barnabas accompany Delirium, and travels from the Earth. Dream then goes back to visit Orpheus, whom he helps to die. Despair, having regretted not going with Delirium, picks some flowers that sprouted from the blood of Orpheus, and gives one to Desire. In his own realm, Dream orders Andros, the custodian of Orpheus' animated head, to bury Orpheus without a marker. Andros is finally shown burying Orpheus' head under a cherry tree with his son and grandson.
|41||Chapter 1||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Alisa Kwitney||Karen Berger|
|42||Chapter 2||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Lisa Aufenanger||Karen Berger|
|43||Chapter 3||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Lisa Aufenanger||Karen Berger|
|44||Chapter 4||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Lisa Aufenanger||Karen Berger|
|45||Chapter 5||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Lisa Aufenanger||Karen Berger|
|46||Chapter 6||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||Lisa Aufenanger||Karen Berger|
|47||Chapter 7||Neil Gaiman||Jill Thompson||Vince Locke / Dick Giordano||Daniel Vozzo||Todd Klein||n/a||Karen Berger|
|48||Chapter 8||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||n/a||Karen Berger|
|49||Chapter 9||Neil Gaiman||Jill Thompson||Vince Locke||Daniel Vozzo||Todd Klein||n/a||Karen Berger|